Morpheeins--a new structural paradigm for allosteric regulation

Trends Biochem Sci. 2005 Sep;30(9):490-7. doi: 10.1016/j.tibs.2005.07.003.


Classic models for the allosteric regulation of protein function consider an equilibrium among protein structures of constant oligomeric multiplicity. The morpheein (mor-phee'-in) concept expands this model to include a dynamic equilibrium of protein structures wherein a protein monomer can exist in more than one conformation and each monomer conformation dictates a different quaternary structure of finite multiplicity and different functionality. The morpheein concept provides a new framework for understanding allosteric regulation, kinetic cooperativity and hysteresis. Porphobilinogen synthase constitutes a prototype morpheein ensemble comprising several interconverting quaternary structure isoforms; one monomer conformation dictates assembly of a high-activity octamer, whereas an alternative monomer conformation dictates assembly of a low-activity hexamer. It is proposed here that the behavior of some other allosteric enzymes reflect dynamic morpheein equilibrium systems and six candidate proteins are enumerated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Allosteric Regulation
  • Kinetics
  • Models, Chemical*
  • Porphobilinogen Synthase / chemistry*
  • Porphobilinogen Synthase / metabolism*
  • Protein Conformation
  • Structure-Activity Relationship


  • Porphobilinogen Synthase